Back
Texte intégral
Journal article

miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

  • Rusca, Nicole Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Dehò, Lorenzo Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Montagner, Sara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Zielinski, Christina E. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Sica, Antonio Istituto Clinico Humanitas, Rozzano, Italy - Dipartimento di Scienze del Farmaco, Universita' del Piemonte Orientale A. Avogadro, Novara, Italy
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Monticelli, Silvia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Show more…
    12.10.2012
Published in:
  • Molecular and cellular biology. - 2012, vol. 32, no. 21, p. 4432-4444
MicroRNA
T lymphocytes
Mast cells
Immunological memory
Activation survival
English The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell memory formation. Increased mast cell survival was due to unbalanced expression of pro- and antiapoptotic factors and particularly to the complete inability of p50- deleted mast cells to induce expression of miR-146a, which in the context of mast cell survival acted as a proapoptotic factor. Interestingly, in a different cellular context, namely, human and mouse primary T lymphocytes, miR-146a and NF-κB p50 did not influence cell survival or cytokine production but rather T cell expansion and activation in response to T cell receptor (TCR) engagement. Our data identify a new molecular network important in modulating adaptive and innate immune responses and show how the same activation-induced microRNA (miRNA) can be similarly regulated in different cell types even in response to different stimuli but can still determine very different outcomes, likely depending on the specific transcriptome.
Language
  • English
Classification
Medicine
License
License undefined
Identifiers
Persistent URL
https://n2t.net/ark:/12658/srd1318847
Statistics
Document views: 57 File downloads:
  • Rusca_MCB_2012.pdf: 139